PD-L1 mRNA and protein expression in canine mammary carcinomas: Correlation with histopathological grade and molecular markers

Vet Pathol. 2024 May;61(3):402-409. doi: 10.1177/03009858241226621. Epub 2024 Jan 28.

Abstract

Programmed death ligand 1 (PD-L1) is an immune checkpoint molecule that plays a crucial role in regulating antitumor immune responses. Canine mammary carcinomas (CMCs) are common tumors of dogs. Despite extensive studies on the heterogeneity of CMCs, there is still a lack of effective precision therapies for the treatment of CMCs. In this study, we aimed to investigate the correlation between PD-L1 mRNA and protein expression in CMCs and explore its association with histopathological grade and molecular markers, including the estrogen receptor, epidermal growth factor receptor 2, and cytokeratin 5/6 (CK5/6). Formalin-fixed paraffin-embedded samples were evaluated for PD-L1 mRNA expression using RNA in situ hybridization and PD-L1 protein expression using immunohistochemistry. We observed no substantial correlation between PD-L1 mRNA and protein expression in CMCs; however, PD-L1 mRNA levels were significantly higher in grade 3 than in grade 1 tumors (P = .001). In addition, we observed a positive correlation between PD-L1 protein expression and CK5/6 expression in CMCs (P = .032). These findings suggest that PD-L1 expression in CMCs is heterogeneous and may be regulated post-transcriptionally. Further studies are needed to explore the prognostic and therapeutic implications of PD-L1 expression in different molecular subtypes of CMCs and their potential as predictive biomarkers for immunotherapy.

Keywords: PD-L1; canine mammary carcinoma; immunohistochemistry; in situ hybridization; molecular markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen* / genetics
  • B7-H1 Antigen* / metabolism
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Dog Diseases* / genetics
  • Dog Diseases* / metabolism
  • Dog Diseases* / pathology
  • Dogs
  • Female
  • Gene Expression Regulation, Neoplastic
  • Immunohistochemistry / veterinary
  • Mammary Neoplasms, Animal* / genetics
  • Mammary Neoplasms, Animal* / metabolism
  • Mammary Neoplasms, Animal* / pathology
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism

Substances

  • B7-H1 Antigen
  • RNA, Messenger
  • Biomarkers, Tumor